WO2005055849A1

WO2005055849A1 - Ultrasonically marked system for therapy delivery

Info

Publication number: WO2005055849A1
Application number: PCT/HR2004/000059
Authority: WO
Inventors: Branko Breyer; Ivo Cikes
Original assignee: Branko Breyer; Ivo Cikes
Priority date: 2003-11-27
Filing date: 2004-11-25
Publication date: 2005-06-23
Also published as: HRP20030990A2

Abstract

The aim of the invention is to enable controlled therapeutic or diagnostic punctures within the heart or other structures in the body that are normally accessible only with catheters or similar devices. The said medical agent may be stem cells, a gene agent, a chemotherapy agent or any type of injectable drug. This system can strictly control the puncture depth. The device consists of a hollow introducer catheter and inside another catheter with a puncture needle. The internal puncture catheter or flexible needle is pushed out to perform a therapeutic or diagnostic puncture. The method for positive ultrasonic localization of a point on an indwelled device, e.g. the said outer or the said inner needle catheter, consists of ultrasonic marking of the catheter and the needle and the use of a transponder to generate a visible mark on the ultrasound scanner screen.

Description

Ultrasonically marked system for therapy delivery

Technical field This invention relates to cardiac therapy, particularly to the guiding apparatus for systems for gene therapy or other pharmaceutical therapy modes. More particularly, the invention pertains to the system for guiding procedures performed with direct application of medical agents directly into the heart muscle or other body structures.

Summary of the invention Control of intracorporeal administration of medical agents is solved by this invention. It enables controlled therapeutic or diagnostic punctures within the heart or other structures in the body that are normally accessible only with catheters or similar devices. The said medical agent may be stem cells, a gene agent, a chemotherapy agent or any type of injectable drug. In a case when implantation is required at a well-defined depth, our invention serves to strictly control this depth. In addition, the placement procedure is guided by ultrasound echography. The puncture is done in two steps. The first step is to bring the puncture set to the right place and in contact with the tissue to be punctured. The second step is the actual puncture with administration of a medical agent or aspiration of a diagnostic sample. Our device consists of a hollow introducer catheter that is the outer guiding means and within it (inside) another catheter with a puncture needle at its distal end. The inside member can be a flexible puncture needle. The introducer catheter is used to maneuver the tip of the device to the point of interest. The internal puncture catheter or flexible needle is than pushed out to perform a therapeutic or diagnostic puncture. Both, the exact positioning and exact puncture need guidance and control to make it essentially safer and more exact compared to an x-ray guided procedure. The method for positive ultrasonic localization of a point on an indwelled device, e.g. the said outer or the said inner needle catheter, consists of ultrasonic marking of the catheter and the use of a transponder to generate a visible mark on the ultrasound scanner screen. Thus, the present method includes an imaging ultrasound scanner and the herewith-described set of ultrasonically marked puncture catheters. One or more miniature piezoelectric marker transducers are mounted at the tip of the outside (introducer) catheter and a separate transducer is mouhted onto the puncture (needled) catheter. The marker transducer electrodes are connected to the electrical conductors that connect it along the catheter to an outside electrical connector at the proximal end of the catheters. When the transducer on the catheter tip is in the scanning area, ultrasound pulses from the transducer of the echoscope energize it. Thus generated high frequency pulses are taken via built-in electrical conductors to the localization transponder. The transponder localization system is a pulse train generator triggered by signal from the said marker transducer when the marked part of the catheter is within the ultrasonic scanning plane or area. When an ultrasonic pulse reaches the marker transducer, the electrical pulse thus induced in it triggers a pulse generator whose output is taken back to the same marker transducer. The marker transducer now becomes an ultrasound transmitter producing a visible signal - mark that marks its position in the echographic image on the screen. The next step in the procedure is the actual controlled puncture. To do this one pushes out the needle and punctures the adjacent tissue. The establishment of the protrusion of the needle into the tissue is done with the said transponder method whereby the needle is ultrasonically marked. The depth of the puncture is done by ultrasound pulse ranging of the distance between the marker transducers on both the introducer catheter and the needled catheter. A separate electronic circuit measures the said distance by measuring the transit time of ultrasound pulses between the said two marker transducers. Thus this invention solves the problem of guidance and control of puncture procedures in the heart. This invention, therefore, comprises the following said devices: the ultrasonically marked introducer catheter through which an ultrasonically marked needled catheter can be moved and the transponder circuits for ultrasound echography guidance as well as the ultrasound pulse ranging circuit. Background and prior art Implantation and positioning of cardiac catheters for therapy delivering is at present mostly facilitated by X-ray imaging methods. The disadvantages of the X- ray methods are the ionizing radiation hazard and poor imaging of soft tissues, e.g. papillary muscles, interventricular septum, cardiac valves etc. Ultrasonic imaging is well suited for soft tissues and presents no X-ray hazard, but has the disadvantage of imaging in one plane tomographically. Using ultrasonic imaging, the flexible leads can be imaged, but the tip or any other part of interest cannot be positively identified since the apparent tip in the image can just be the point at which the lead leaves or enters the scanning plane. Ultrasonography has therefore fairly rarely been used for cardiac catheters imaging. The use was limited to some sonographically suitable circumstances and to pregnancy where X-ray imaging is not recommended. In order to improve the localization of electrodes and catheter tips on the cardiac leads we developed ultrasonically marked catheters and leads. Various approaches to guiding intracardiac and Minimum Invasive Surgery (MIS) procedures have been proposed.

Attempts have been made to make a MIS device sensitive to ultrasound by using the needle as a solid ultrasound wave-guide as per US Pat no. 4,431,006 to Trimmer, Garduineer, Hadjikostis. This works only for solid, basically non-flexible devices.

A transducer mounted at the tip of a flexible MIS device for ultrasound Doppler measurements as per US Pat no. 4,771 ,788 to Millar can be used to intraluminally detect blood flow velocity. Similarly a device with an ultrasound ranging device in US Pat no. 5,893,848 to Negus, Linhares, Rudko and Woodruff might be used to determine the depth of lesions induced by MIS, similar to forward looking ultrasound echo-ranging transducer from US Pat no. 6,024,703 to Zanelli, Giba, Davis, Murphy-Chutorian as well as in US Pat no. 6,086,534 to Kesten. Other axial ranging systems include the annular piezoelectric transducer as per US Pat no. 6024703 to Zanelli, Giba, Davis and Murphy-Chutorian. In the US Pat no 6,206,831 and 6,508,765 to Suorsa, Swanson, Panescu, TenHoff and Whayne ultrasound transducers are used both for ultrasonic ablation and for distance measurement. Performance of all these ranging devices for guidance strongly depends on individual interpretation of A-mode onscreen images.

Attempts have been made to combine ultrasound scanning imaging probes with MIS devices as per US Pat no 5,024,234 to Leary and McKenzie. A similar concept from the standpoint of guidance can be found in US Pat no. 5,409,000 to Imran. Very high frequency ultrasound scanning probes combined with laser therapy devices have been devised in US Pat no 5,109,859 to Jenkins. In US Pat no. 6,546,276 to Zanelli the distance and alignment with the heart wall is measured using a multitude of ultrasound transducer elements mounted at the perimeter near the tip of a MIS device. These devices are too expensive to be disposable and yield only side view. Therefore these devices can have a very narrow field of applications within the scope of the problem we are solving.

X-ray equipment may be used for the navigation in conjunction with a specific dispenser of radio opaque markers, as per US Pat no. 6,030,377 to Linhares, Negus, Rudko and Woodruff but our intention is to avoid ionizing radiation.

In US Pat no 6216027 and US Pat no. 6,490,474 to Willis, Brisken, Zeng and Hurd reference ultrasound transducers are positioned within the patient's heart and other marker transducers are than used to determine the position of the marker transducers by triangulation and thus guide certain in-heart procedures. A considerable number of devices must thus be indwelled in the heart, which makes it less practical a solution for our purposes.

Our solution to the problem is based on the application of the concept of ultrasound scanners in conjunction with ultrasonically marked catheters and MIS devices. Ultrasound scanners are presently available in almost all physicians' offices and in all hospitals. Langberg (JACC Vol.12, No.1 , July 1988:218-23) teaches how to localize the catheter and its electrode within the heart by utilizing our invention described in our US Patents 4,697,595 and 4,706,681 , as clearly cited by him at the introduction and in the references though not citing these patent references. In our US Patent no.5,840,030, we show how to use directional ablation field with an indirect method of "energy visualization" within the echocardiographic image by knowing the directivity relation between the two fields: ultrasonic field and ablation field and how to monitor the electrode contact with the tissue. In US Patent No. 5,385,148 Lesh shows how to ultrasonically characterize the tissue. The localization function can be accomplished in two ways: either by using a transponder or by using a passive localization system. The transponder is triggered by signals from the marker transducer routed through the lead. Upon triggering, the transponder generates a characteristic series of electrical pulses, which are taken back to the same marker transducer, which, therefore, transmits a series of ultrasound pulses. These pulses appear at the echograph screen as a visible mark adjacent to the marked part of the lead irrespective of whether the lead itself is clearly discernible or not. The mark appears along the line-of-sight of the scanner as a white blinking pattern. The passive localization system comprises a time doubling circuit (TDC) which doubles the time elapsed between the transmission of an ultrasound pulse from the scanner probe and its reception by the marker transducer and then triggers a mark signal generator. This signal is taken to the signal bus of the ultrasonic scanner in the desired shape, polarity and time sequence. The system comprises medical grade isolation circuits for electrical shock safety according to the IEC 601-1 standard for CF class equipment. Accuracy of the localization depends on the physical dimensions and positioning of the marker transducer as well as on the beam width and sensitivity of the system. With the presently available piezoelectric transducers, the length of the marker transducer can be reduced to 1.5mm, yielding, with the present design a lengthwise positioning error of about 2mm. In cardiac catheter applications one normally needs only one mark shape, but in electrophysiology applications one must have multiple mark forms for discerning the different electrodes. A passive system has a greater flexibility in this respect than the transponder. The passive system is scanner-specific in design. The ultrasonic marking system can help in avoiding a significant part of the use of X-rays in cardiac catheterization and lead implantation or electrophysiological studies. In addition it could help detection of the lead malfunctions. The radiation dose to the hands of the operator can easily reach 300 micro grays per application so that trying to avoid the use of X-rays when possible is justified. These and other aspects were pertinently described in our scientific papers B. Breyer, B. Ferek-Petric & I. Cikes. Properties of Ultrasonically Marked Leads. Pacing and Clinical Electrophysiology. Vol.12, (1989), p.1369., and B.Breyer & B. Ferek-Petric. Possibilities of Ultrasound Catheters. Int.Journ. of Cardiac Imaging, Vol.6., (1991), p. 277.

Disclosure of the invention It is the principal object of this invention to enable exact control over the direction and depth of therapeutic or diagnostic punctures within the heart or other structures in the body that are normally accessible only with catheters or similar devices. This puncture may serve to administer some medical agent into the punctured tissues. The said agent may be stem cells, a gene agent, a chemotherapy agent or any type of injectable drug. In a case when implantation is required at a well-defined depth, our invention serves to strictly control this depth. The advantage of the diagnostic aspect of such a puncture is again the strict control over the puncture depth. Another object of this invention is to guide and localize exact points of delivery of medical therapy that is performed by injection or instillation of some medical agent directly into human tissues in places within the body that are not visible or cannot be made visible by optical means but can be imaged by ultrasound echography. The puncture is done in two steps, namely, the first step is to bring the puncture set to the right place and in contact with the tissue to be punctured, and the second step is the actual puncture with administration of a medical agent or aspiration of a diagnostic sample. The said puncture is done with a specific set of puncture catheters. It consists of a hollow introducer catheter and within it (inside) another catheter with a puncture needle at its distal end. The inside member can be a flexible puncture needle. The introducer catheter is used to maneuver the tip of the device to the point of interest. The internal puncture catheter or flexible needle is than pushed out to perform a therapeutic or diagnostic puncture. Both, the exact positioning and exact puncture need guidance and control to make it essentially safer and more exact compared to a blind procedure. Guidance by x-rays is not completely adequate due to radiation hazard and due to the fact that soft tissues are poorly imaged by this method. Ultrasound scanning presents no radiation hazard to the patient and the medical staff and has superior soft tissue imaging capability. The visualization of the said catheter end and puncture needle tip is essential for ultrasonic guidance of said procedures with the puncture catheter set. The method for positive ultrasonic localization of a point on an indwelled device, e.g. the said outer or the said inner needle catheter, consists of ultrasonic marking of the catheter and the use of a transponder to generate a visible mark on the ultrasound scanner screen. This means that the present method includes an imaging ultrasound scanner and the herewith-described set of ultrasonically marked puncture catheters. One or more miniature piezoelectric marker transducers are mounted at the tip of the outside (introducer) catheter and a separate transducer is mounted onto the puncture (needled) catheter. The marker transducer electrodes (fired-on silver or similar) are connected to the electrical conductors that connect it along the catheter to an outside electrical connector at the proximal end of the catheters. When the transducer on the catheter tip is in the scanning area, ultrasound pulses from the transducer of the echoscope energize it. Thus generated high frequency pulses are taken via built-in electrical conductors to the localization electronic circuit. The most straightforward electronic circuitry for the purpose of the localization is a transponder. The transponder localization system is a pulse train generator triggered by signal from the said marker transducer when the marked part of the catheter is within the ultrasonic scanning plane or area. When an ultrasonic pulse reaches the marker transducer, the electrical pulse thus induced in it triggers a pulse generator whose output is taken back to the same marker transducer. The marker transducer now becomes an ultrasound transmitter producing a visible signal - mark that marks its position in the echographic image on the screen. The method does not depend on whether the scanning is done in two or in three dimensions. By this procedure the first task of bringing the puncture catheter into position is accomplished. The next step in the procedure is the actual controlled puncture. To do this one pushes out the needle and punctures the adjacent tissue. The fact that the puncture has been performed must be established and the puncture depth must be measured. The establishment of the protrusion of the needle into the tissue is done with the said transponder method whereby the needle is ultrasonically marked. The depth of the puncture is done by ultrasound pulse ranging of the distance between the marker transducers on both the introducer catheter and the needled catheter. A separate electronic circuit measures the said distance by measuring the transit time of ultrasound pulses between the said two marker transducers. Thus the puncture depth is closely controlled. Thus this invention solves the problem of guidance and control of puncture procedures in the heart. This invention, therefore, comprises the following said devices: the ultrasonically marked introducer catheter through which a ultrasonically marked needled catheter can be moved and the transponder circuits for ultrasound echography guidance as well as the ultrasound pulse ranging circuit.

Brief description of the drawings Referring to figure 1: The septum is punctured using a puncture catheter set that is introduced into the right heart ventricle. The introducer catheter 1 marked with the marker transducer 2 is positioned in the right heart. Through this introducer catheter, another catheter, the needle catheter 11 marked with the marker transducer 12 is introduced and the needle 13 is pushed forward and thus punctures a heart structure 10, in this case the interventricular septum. Referring to figure 2: The hollow catheter 1 is marked with a transducer 2 that is connected to the proximal side of the catheter 1 with lengthwise conductors 3 and 4. Another, internal catheter 11 with a puncturing needle 13 at its tip is marked with a piezoelectric marker transducer 12. Lengthwise conductors 5 and 6 connect the marker transducer 12 to the proximal side of the catheter 11.

Referring to figure 3: The hollow catheter 1 is marked with a transducer 2 that is connected to the proximal side of the catheter 1 with lengthwise conductors 3 and 4. Another, internal catheter 111 with a puncturing needle 13 at its tip is marked with a piezoelectric marker transducer 12. Lengthwise conductors 105 and 106 connect the marker transducer 12 to the proximal side of the catheter 111.

Referring to figure 4: The ultrasound scanner 30 is used for imaging of the interior of the patient's body 33. The scanner probe 34 scans an 35 area within the patient's body. The said catheter 1 is inserted into the body and connected to the marking circuitry 37, e.g. transponders. The catheter set as described in figures 1. 2, 3 is marked with the marker transducers 2 and 12. When the said marker transducers 2 or 12 are within the imaged area 35 the marking circuitry 37 generates such electrical signals as to generate visible and recognizable marks on the screen of the ultrasound scanner 30.

Referring to figure 5: The marking circuitry is double if there are two marking transducers as illustrated in figures 1 and 2. As illustrated in figure 5, the circuitry consists of two transponders or equivalent circuits 42 and 44 and ranging parts 41 and 43. These are interconnected with appropriate switching circuitry 45 and to the catheter set 1 from figures 1 , 2, 3, 4 via switching and connection circuitry 47. A controlling circuit 46 is used to coordinate the operation of the separate parts.

Referring to figure 6: The marking circuitry can have a multiplexer switch 55 to operate as double if there are two marking transducers 2 and 12 as illustrated in figures 1 and 2. As illustrated in figure 6, the circuitry consists of one transponder 52 and ranging circuits 51 and 56. These are interconnected with appropriate switching circuitry 55 and to the catheter set 1 from figures 1, 2, 3, 4 via switching and connection circuitry 57 and 58. A controlling circuit 55 is used to coordinate the operation of the separate parts.

Description of preferred embodiments As illustrated in figure 1 , the problem to be solved is guidance and control of puncture of some structure within the living heart. The guidance means bringing the device up to the desired structure in the body. The control means that the puncture procedure is controlled by close control of the depth of the puncture as measured from the surface of the structure. The puncture can be diagnostic or therapeutic. Therapeutic punctures include delivery of gene therapy, chemotherapy of delivery of any other medical agent. An outer guiding means in the form of a flexible catheter 1 containing another flexible puncture catheter or needle 11 is indwelled and positioned at a point of interest 10, in the illustrated case the interventricular septum. The practical problem is the control of this positioning. This is done using an ultrasound scanner with which one can, in real time, see both the soft tissue structures of the heart and the said catheters. However, due to the continuous movement and small dimensions of the said devices the exact position of the tip that contains the needle 13 is hard to know without the present technological invention. In order to solve this problem a marker transducer 2 is mounted onto the outer catheter 1 and another marker transducer 12 is mounted onto the internal device 11. This internal device 11 is axially movable within the outer catheter 1 and can be pushed such as to expose the puncture needle 13, thus puncturing the structure of interest 10. An external ultrasound echo scanner and a transponder are used in conjunction with the said catheter assembly. The said catheters are in more detail illustrated in figures 2 and 3. In the embodiment shown in figures 2A and 2B the outer catheter 1 is of the steerable kind so its distal part can be bent in at least one axis using outside controls. As seen in figure 2A, a piezoelectric transducer 2 is mounted adjacent to the tip of catheter 1. This transducer, that can be a composite transducer made up of a multitude of transducers is connected the proximal part of the catheter by electrical conductors 3 and 4 and can deliver and accept electrical signals to and from electronic circuitry connected to it. Another catheter 11 of smaller diameter is positioned within the catheter 1 and can fully be retracted into it. It bears a puncture needle 13 or other device on its tip. The needle is shown as protruding from the outer catheter 1 , but during maneuvering within the body the needle can fully be retracted so that it does not penetrate anything until the ultimate target is reached. Once the target is reached the therapeutic or diagnostic puncture can be effected by pushing the inner catheter 11 out (figure 2B), thus exposing the needle 13 that penetrates the tissue in front of the device. At the same time a second marker transducer 12 is exposed and can deliver and accept electrical signals to and from electronic circuitry connected to it via internal electrical conductors 5 and 6 that lead to the proximal side of the said catheter 11 and can be connected to appropriate circuitry that we shall describe later. The needle 13 is a hollow needle that is used for therapeutic punctures to deliver medical agents via the hollow catheter 11 through the hollow needle 13 into the bodily structure 10 to be treated. In the embodiment illustrated in figures 3A and 3B the outer catheter 1 is of the steerable kind so its distal part can be bent in at least one axis using outside controls. As seen in figure 3A, a piezoelectric transducer 2 is mounted adjacent to the tip of catheter 1. This transducer, that can be a composite transducer made up of a multitude of transducers is connected the proximal part of the catheter by electrical conductors 3 and 4 and can deliver and accept electrical signals to and from electronic circuitry connected to it. Another catheter 111 of smaller diameter is positioned within the catheter 1 and can fully be retracted into it. It can be pushed out to the side from the catheter 1. It bears a puncture needle 13 or other device on its tip. The needle is shown as protruding from the outer catheter 1 , but during maneuvering within the body the needle can fully be retracted so that it does not penetrate anything until the ultimate target is reached. Once the target is reached the therapeutic or diagnostic puncture can be effected by pushing the inner catheter 111 out (figure 2B), thus exposing the needle 13 that penetrates the tissue at the side of the device. At the same time a second marker transducer 12 is exposed and can deliver and accept electrical signals to and from electronic circuitry connected to it via internal electrical conductors 5 and 6 that lead to the proximal side of the said catheter 111 and can be connected to appropriate circuitry that we shall describe later. The needle 13 is a hollow needle that is used for therapeutic punctures to deliver medical agents via the hollow catheter 111 through the hollow needle 13 into the bodily structure 10 to be treated. This procedure can be used in cases when the structure to be treated is better accessed by leaning the steerable catheter 1 against it or when this structure is narrow, e.g. a blood vessel. The said puncture procedures are guided and controlled using outside ultrasound echo scanner means and a dedicated localization circuitry as illustrated in figure 4. The ultrasound scanner 30 images the area 35 within the human body 33. The said catheter assembly 1 which is the outer guiding means that is described with the help of figures 1, 2, 3 is indwelled in the body. Among other parts already described it bears two piezoelectric marker transducer assemblies 2 and 12 that are connected to electronic circuits 37 and 38 via conductors within the catheter assembly. When ultrasound pulses from the scanner probe 34 hit the piezoelectric marker transducers 2 and 12 electrical signals are generated and taken to the circuit 37 that is preferably a transponder. A transponder is a device that generates a characteristic electrical signal upon reception of a signal from a piezoelectric transducer and sends this characteristic electrical signal, called the signature, back to the transducer from which it was triggered. The electronic circuitry used in this invention is adapted to the two different tasks that need to be accomplished by the present device, namely the guidance of the device to its intended position and control of the puncture procedure. In accordance with the first aspect of this invention the catheter assembly 1 is guided to the desired position by the use of the outside ultrasound scanner 30 in conjunction with a transponder 37 or other equivalent positioning circuit. In accordance with the second aspect of this invention, the depth and success of the puncture is determined and controlled by measurement of the distance between the said marker transducers 2 and 12 using ultrasound pulse ranging circuitry 38. In more detail, there are various possibilities for embodiment of the outlined basic principle. As illustrated in figure 5 it is possible to use two transponders 42 and 44 that are connected to the marker transducer 2 and 12 respectively. These are connected via the switch 45 during the guidance phase. Each of the said transponders generates its own electric and consequently a characteristic ultrasound pulse burst called the signature. These different signatures yield different marks on the screen of the scanner 30. Once the point of interest is reached and the catheter 1 leans against it, the second catheter 11 is pushed out so that the needle 13 penetrates the tissue, e.g. cardiac ventricular septum. The depth the needle penetrates is controlled by measurement of the distance between the marker transducers 2 and 12. For this purpose the two transducers are switched over to ranging circuits 41 and 43 via the switch 45 and under the control of the controlling circuitry 46 that can be manipulated by the operator. This ultrasound pulse ranging circuitry essentially measures ultrasound pulse transit time and is known in the art. The marker transducers can be switched 45 back and forth between the said two sets of electronic circuits at will. It is possible to use a single transponder as illustrated in figure 6. In this case a single transponder 52 is used and switched back and forth between marker transducers 2 and 12 using the switch 57. The controller 53 controls the rate of the switching between the two transducers. Once the point of interest is reached and the catheter 1 leans against it, the second catheter 11 is pushed out so that the needle 13 penetrates the tissue, e.g. cardiac ventricular septum. The depth the needle penetrates is controlled by measurement of the distance between the marker transducers 2 and 12. For this purpose the two transducers are switched over to ranging circuits 51 and 56 via the switches 55 and 58 respectively and under the control of the controlling circuitry 53 that can be manipulated by the operator. This ultrasound pulse ranging circuitry essentially measures ultrasound pulse transit time and is known in the art. The marker transducers can be switched back and forth between the said two sets of electronic circuits using switching circuits 55, 57, 58. The previously mentioned objects of guiding the active tip of the device for delivery of medical agent to the bodily structure of interest and subsequent control of the puncture procedure for the said delivery are thus achieved.

Claims

1. Ultrasonically marked system for therapy delivery, comprising an outer ultrasonically marked guiding device means adapted for implantation into the human body, said outer guiding device means comprising an inner ultrasonically marked therapy administration device means, said therapy administration device means being adapted to penetrating the surrounding tissue and for delivery of a therapeutic medical agent within said tissue, whereby the selected guiding device point of interest and the selected therapy administration device point of interest are visible as marks within the image of an ultrasound echographic scanner means.

2. Ultrasonically marked system for therapy delivery of claim 1 , comprising means for sliding the said inner therapy administration device means within the body of said outer guiding device means thereby positioning said therapy administration device point of interest either within the body of said outer guiding device means, or said therapy administration device point of interest protruding out of the body of said outer guiding device means.

3. Ultrasonically marked system for therapy delivery of claim 1 , wherein said outer guiding device means comprises a first ultrasonic transducer means mounted fixed on the body of said outer guiding device means at the position of said outer guiding device point of interest and said inner therapy administration device means comprises a second ultrasonic transducer means mounted fixed adjacent to the position of said therapy administration device point of interest whereby said second ultrasonic transducer means may be either positioned within the body of said outer guiding device means or said second ultrasonic transducer means protruding out of the body of said outer guiding device means.

4. Ultrasonically marked system for therapy delivery of claim 1 , comprising means for rendering point of interest of said outer ultrasonically marked guiding device means visible within the image of said echographic scanner means whenever the scanning plane or scanning area of said echographic scanner means intersects said guiding device point of interest.

5. Ultrasonically marked system for therapy delivery of claims 3 and 4, comprising means for rendering said first transducer means visible within the image of said echographic scanner means whenever the scanning plane or scanning area of said echographic scanner means intersects said first transducer means.

6. Ultrasonically marked system for therapy delivery of claim 5 wherein said first transducer means is mounted adjacent to the tip of said outer guiding device means thereby marking the said guiding device tip and enabling the said guiding device tip position control within the echographic image.

7. Ultrasonically marked system for therapy delivery of claim 2, comprising means for rendering of said therapy administration device point of interest visible within the image of said echographic scanner means whenever the said therapy administration device means protrudes out of the said guiding device means, thereby exposing said therapy administration device point of interest out of the body of said outer guiding device, and the scanning plane or scanning area of said echographic scanner means intersects said therapy administration device point of interest.

8. Ultrasonically marked system for therapy delivery of claim 3, comprising means for rendering of said second transducer means visible within the image of said echographic scanner means whenever the said therapy administration device means protrudes out of the said guiding device means, thereby exposing said second transducer means, and the scanning plane or scanning area of said echographic scanner means intersects said second transducer.

9. Ultrasonically marked system for therapy delivery of claim 8 wherein said second transducer means is mounted at the tip of said therapy administration device means thereby marking the said therapy administration device tip and enabling the said therapy administration device tip position control within the echographic image.

10. Ultrasonically marked system for therapy delivery of claim 3, comprising means for making said first transducer of said guiding device means and said second transducer of said therapy administration device being visible within the image of said echographic scanner means as two separate marks whenever said therapy administration device protrudes out of the body of said guiding device means thereby exposing said second ultrasonic transducer and the scanning plane or area of said echographic scanner means intersects both said ultrasonic transducers.

11. Ultrasonically marked system for therapy delivery of claim 10, comprising means for measurement of the distance between the two said marks on the image of said echographic scanner means or using a separate ultrasound ranging apparatus thereby precisely monitoring the puncture into the surrounding tissue.

12. Ultrasonically marked system for therapy delivery of claim 11 , wherein said ranging apparatus is an ultrasonic pulse range system that measures the distance between the said ultrasound transducer means by measuring the time necessary for ultrasound to travel between the two said transducers.

13. Ultrasonically marked system for therapy delivery of claim 1 , comprising an outer ultrasonically marked cardiac catheter means intended for implantation into the human heart or its vessel, said outer cardiac catheter means comprising an inner ultrasonically marked injection needle that can be extended out of the said cardiac catheter means for puncturing the cardiac muscle and delivery of a therapeutic medical agent within said cardiac muscle, whereby selected cardiac catheter point of interest and selected point of interest of the said needle are visible as marks within the cardiac image of an echocardiographic scanner means.

14. Ultrasonically marked system for therapy delivery of claim 13, comprising means for sliding the said inner needle means within the body of said outer cardiac catheter means whereby said needle point of interest may be either within the body of said outer cardiac catheter means or protruding out of the body of said outer cardiac catheter means.

15. Ultrasonically marked system for therapy delivery of claim 13, wherein said outer cardiac catheter means comprises a first ultrasonic transducer means mounted fixed on the body of said outer cardiac catheter means at the position of said outer cardiac catheter point of interest and said inner needle means comprises a second ultrasonic transducer means mounted fixed adjacent to the position of said needle point of interest whereby said second ultrasonic transducer means may be either within the body of said outer cardiac catheter means or protruding out of the body of said outer cardiac catheter means.

16. Ultrasonically marked system for therapy delivery of claim 13, comprising means for rendering point of interest of said outer ultrasonically marked cardiac catheter means visible within the image of said echocardiographic scanner means whenever the scanning plane or scanning area of said echocardiographic scanner means intersects said cardiac catheter point of interest.

17. Ultrasonically marked system for therapy delivery of claims 15 and 16, comprising means for rendering said first transducer means visible within the image of the heart obtained by said echographic scanner means whenever the scanning plane or scanning area of said echographic scanner means intersects said first transducer means.

18. Ultrasonically marked system for therapy delivery of claim 17 wherein said first transducer means is mounted at the tip of said outer cardiac catheter means.

19. Ultrasonically marked system for therapy delivery of claim 14, comprising means for rendering of said needle point of interest visible within the heart image of said echocardiographic scanner means whenever the said needle means protrudes out of the said cardiac catheter means, thereby exposing said needle point of interest out of the body of said outer cardiac catheter, and the scanning plane or scanning area of said echocardiographic scanner means intersects said needle point of interest.

20. Ultrasonically marked system for therapy delivery of claim 15, comprising means for rendering of said second transducer means visible within the heart image of said echocardiographic scanner means whenever the said needle means protrudes out of the said cardiac catheter means, thereby exposing said second transducer means, and the scanning plane or scanning area of said echocardiographic scanner means intersects said second transducer.

21. Ultrasonically marked system for therapy delivery of claim 20 wherein said second transducer means is mounted at the tip of said needle means.

22. Ultrasonically marked system for therapy delivery of claim 13, comprising means for making said first transducer of said cardiac catheter means and said second transducer of said needle being visible within the heart image of said echocardiographic scanner means as two separate marks whenever said needle protrudes out of the body of said cardiap catheter means thereby exposing said second ultrasonic transducer, and the scanning plane or area of said echographic scanner means intersects both said ultrasonic transducers.

23. Ultrasonically marked system for therapy delivery of claim 22 comprising means for measurement of the distance between the two said marks on the image of said echographic scanner means or using a separate ultrasound ranging apparatus thereby precisely monitoring the puncture into the cardiac muscle.

24. Ultrasonically marked system for therapy delivery of claim 23, wherein said ranging apparatus is an ultrasonic pulse range system that measures the distance between the said ultrasound transducer means by measuring the time necessary for ultrasound to travel between the two said transducers.

25. Ultrasonically marked system for therapy delivery of claim 23 where the distance among the said transducers can continuously be monitored by the said ultrasound ranging apparatus.

26. Ultrasonically marked system for therapy delivery of claim 13, comprising means for ultrasonic monitoring of the contact between said cardiac catheter means and cardiac muscle.

27. Ultrasonically marked system for therapy delivery of claims 3 and 15, wherein said first transducer means is electrically connected to the first ultrasonic transponder means.

28. Ultrasonically marked system for therapy delivery of claims 3 and 15, wherein said second transducer means is electrically connected to the second ultrasonic transponder means.

29. Ultrasonically marked system for therapy delivery of claims 27 and 28, wherein said first ultrasonic transponder means generates an electric pulse thereby energizing said first ultrasonic transducer means that consequently transmits the ultrasonic pulse instantly upon reception of the ultrasonic wave emitted by said ultrasonic echoscope means and consequent reception of electric pulse within said first transponder means.

30. Ultrasonically marked system for therapy delivery of claim 29, wherein second transponder means is transiently switched off during the electric pulse transmission of said first transponder in order to prevent reception within said second transducer means of the ultrasonic wave transmitted by said first transducer means.

31. Ultrasonically marked system for therapy delivery of claims 27 and 28, wherein said second ultrasonic transponder means generates an electric pulse thereby energizing said second ultrasonic transducer means that consequently transmits the ultrasonic pulse instantly upon reception of the ultrasonic wave emitted by said ultrasonic echoscope means and consequent reception of electric pulse within said second transponder means.

32. Ultrasonically marked system for therapy delivery of claim 31 , wherein first transponder means is transiently switched off during the electric pulse transmission of said second transponder in order to prevent reception within said first transducer means of the ultrasonic wave transmitted by said second transducer means.

33. Ultrasonically marked system for therapy delivery of claims 29 to 32, wherein said two transponders operate in mutually exclusive mode in such a way as to prevent that said first transducer receives the signal transmitted by said second transducer and vice versa that said second transducer receives the signal transmitted by said first transducer.

34. Ultrasonically marked system for therapy delivery of claims 3 and 15, wherein said first transducer means and said second transducer means are electrically connected to the ultrasonic transponder means via an alternate switch means in such a way as to alternatively connect either said first transducer means to said transponder means or said second transducer means to said transponder means.

35. Ultrasonically marked system for therapy delivery of claim 34, wherein said switching in alternative connection between said first transducer and said transponder and between said second transducer and said transponder yields two blinking markers within the image of said ultrasonic echoscope means.

36. Ultrasonically marked system for therapy delivery of claim 35, wherein said two blinking markers designate the position of both ultrasonic transducers respectively.

37. Ultrasonically marked system for therapy delivery of claim 36 wherein the blinking markers have different shape, or different color, or different signature.

38. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent is a gene.

39. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent is RNAi.

40. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent is a protein.

41. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent is a cytostatic.

42. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent are myocytes.

43. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent is ethanol.

44. Ultrasonically marked system for therapy delivery of claims 1 and 13, wherein said therapeutic medical agent are stem cells.

45. Ultrasonically marked system for therapy delivery of claims 3 and 15 wherein said needle slides forward out of the said outer cardiac catheter thereby first transducer means and second transducer means having approximately same mutual angular orientation of their ultrasonic directivity functions.

46. Ultrasonically marked system for therapy delivery of claims 3 and 15 wherein said needle slides sidewise out of the said outer cardiac catheter thereby first transducer means and second transducer means having different mutual angular orientation of their ultrasonic directivity functions.

47. Ultrasonically marked system for therapy delivery of claim 46 wherein said ultrasonic directivity function of the said second transducer means changes the angle of its ultrasonic directivity function relatively to the ultrasonic directivity function of second transducer means as the therapy administration device slides out of the said outer cardiac catheter.

48. A method of a therapy delivery, comprising:

(a) an implantation of a guiding device means into the human body, whereby said guiding device means comprises a means for ultrasonic marking of its tip within the image of an echographic scanner means whenever the scanning plane of said scanner means intersects the tip of said guiding device means thereby enabling precise positioning of said guiding device means into an anatomic location wherein the therapy is to be delivered, said guiding device means comprising within it a movable therapy administration device for penetrating the surrounding tissue, said therapy administration device comprising means for marking of its tip within the image of said scanner means whenever the scanning plane of said scanner means intersects the therapy administration device, thereby enabling visual control of the penetration within the tissue and control of therapy delivery utilizing said image.

(b) Penetrating the surrounding tissue under echographic guidance whereby first marker is visible within the echographic image pointing to the tip of said guiding device and second marker is visible within the echographic image pointing to the tip of said therapy administration device.

(c) Administering of a therapeutic medical agent through said therapy administration device into the said surrounding tissue.

49. A method of a therapy delivery of claim 48 that includes ultrasonic monitoring of the contact between said guiding device means and the surrounding tissue.

50. A method of a therapy delivery of claim 48 that includes measurement of the mutual distance between the ultrasonic markers of said guiding device means and the ultrasonic marker of said therapy administration device.

51. A method of a therapy delivery of claim 48 that includes implantation of said guiding device means into the heart or its vessel.

52. A method of a therapy delivery to the heart of claim 51 , whereby said guiding device means comprises an therapy administration device for puncturing the cardiac muscle, said therapy administration device comprising means for ultrasonically marking of its tip by means of an ultrasonic transducer means.

53. A method of a therapy delivery of claim 52 that includes monitoring of the contact between said guiding device means and rhythmically moving endocardium.

54. A method of a therapy delivery of claim 48 that includes two transponders - first and second, whereby said ultrasonic transducer means of said guiding device is connected to said first transponder and said ultrasonic transducer means of said therapy administration device is connected to said second transponder.

55. A method of a therapy delivery of claim 54, wherein reception of ultrasonic signal in one of said transponders triggers an instant transmission of an ultrasonic signal out of same said transponder whereby reception of the signal during transmission of said ultrasonic signal is disabled in both said transponders.

56. A method of a therapy delivery of claim 48, comprising one transponder, whereby said ultrasonic transducer means of said guiding device and said ultrasonic transducer means of said therapy administration device are alternatively connected to said transponder via switch means.

57. A method of a therapy delivery of claim 48, wherein said guiding device means is a cardiac catheter.

58. A method of a therapy delivery of claim 48, wherein said guiding device means is an actuator or an arm of a surgical robot.

59. A method of a therapy delivery of claim 48, wherein said therapy administration device is a puncturing needle.

60. A method of a therapy delivery of claim 48, wherein said therapy administration device is a therapy applicator of a surgical robot.

61. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent is a gene.

62. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent is RNAi.

63. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent is a protein.

64. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent is a cytostatic.

65. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent are myocytes.

66. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent are stem cells.

67. A method of a therapy delivery of claim 48, wherein said therapeutic medical agent is ethanol.